Biology subjects

Snider, S. B.

Publications and source records attributed to Snider, S. B..

4 recordsLinked to original sources

bioRxiv2026

A Brain Circuit for Status Epilepticus

Status epilepticus (SE) is a life-threatening persistent epileptic seizure that can arise from various brain structures, leaving its brain circuit unknown. In this study, we utilize brain imaging changes during SE to reveal the brain architecture and circuit of persistent seizures. Multimodal lesion mapping identified that brain imaging changes during SE localize to a specific predisposed brain architecture characterized by increased metabolic rate, high synaptic and mitochondrial density, glutamate (mGLUR5 and NMDA) and GABA receptors. Gene expression patterns within lesion locations revealed a transcriptomic profile enriched for epilepsy pathologies (including SE), neuronal and synaptic processes, and glutamate signaling. Lesion network mapping demonstrated these same lesions map to a common brain circuit, unifying a traditionally heterogeneous patient population. Findings were validated in an independent cohort and the identified SE circuit distinguished brain imaging changes during SE from other lesion etiologies with excellent accuracy (91%), significantly outperforming all other tested maps. With this SE circuit, we identify therapeutic targets for precision therapy that could modulate this circuit. This study demonstrates brain imaging changes in SE converge on a unified brain circuit that could help diagnostic workup of patients in critical care and guide clinical trials of precision therapy for persistent seizures.

neuroscience↗

bioRxiv2026

The methodological foundations of lesion network mapping remain sound

Lesion network mapping (LNM) and related techniques have been used in over 200 studies, primarily to test whether anatomically distributed lesions that cause the same symptom fall within a common brain network. A recent article1 challenges the specificity and validity of this technique, suggesting that lesion network maps primarily reflect intrinsic properties of the normative connectome rather than lesion-symptom relationships. However, the data and procedures in van den Heuvel et al. do not reflect those used in most LNM studies. Further, the main conclusions were based on similarity between maps, but similarity does not imply the absence of meaningful differences. In contrast, LNM provides evidence for meaningful differences using specificity testing. Exemplary analyses of 1090 lesion locations from 34 prior LNM studies do not support van den Heuvels concerns and confirm the lesion-deficit specificity of LNM. While we encourage further methodological investigation, the analyses of van den Heuvel et al. do not invalidate prior LNM findings or future applications.

neuroscience↗

bioRxiv2023

Sustaining wakefulness: Brainstem connectivity in human consciousness

Consciousness is comprised of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that modulate awareness in the human brain, but knowledge about the subcortical networks that sustain arousal is lacking. We integrated data from ex vivo diffusion MRI, immunohistochemistry, and in vivo 7 Tesla functional MRI to map the connectivity of a subcortical arousal network that we postulate sustains wakefulness in the resting, conscious human brain, analogous to the cortical default mode network (DMN) that is believed to sustain self-awareness. We identified nodes of the proposed default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain by correlating ex vivo diffusion MRI with immunohistochemistry in three human brain specimens from neurologically normal individuals scanned at 600-750 {micro}m resolution. We performed deterministic and probabilistic tractography analyses of the diffusion MRI data to map dAAN intra-network connections and dAAN-DMN internetwork connections. Using a newly developed network-based autopsy of the human brain that integrates ex vivo MRI and histopathology, we identified projection, association, and commissural pathways linking dAAN nodes with one another and with cortical DMN nodes, providing a structural architecture for the integration of arousal and awareness in human consciousness. We release the ex vivo diffusion MRI data, corresponding immunohistochemistry data, network-based autopsy methods, and a new brainstem dAAN atlas to support efforts to map the connectivity of human consciousness. One sentence summaryWe performed ex vivo diffusion MRI, immunohistochemistry, and in vivo 7 Tesla functional MRI to map brainstem connections that sustain wakefulness in human consciousness.

neuroscience↗

bioRxiv2019

Optimizing the Accuracy of Cortical Volumetric Analysis in Traumatic Brain Injury

Cortical volumetric analysis is widely used to study the anatomic basis of neurological deficits in patients with traumatic brain injury (TBI). However, patients with TBI-related lesions are often excluded from analysis, because cortical lesions may compromise the accuracy of reconstructed surfaces upon which volumetric measurements are based. Here, we propose a novel FreeSurfer-based lesion correction method and illustrate its impact on cortical volume measures in patients with chronic moderate-to-severe TBI. We performed MRI in 87 patients at mean+/-SD 10.9+/-9.1 years post-injury using a T1-weighted multi-echo MPRAGE sequence at 1 mm resolution. Following surface reconstruction, we parcellated the cerebral cortex into seven functional networks using FreeSurfers standard pipeline. Next, we manually labeled vertices on the cortical surface where lesions caused inaccuracies and removed them from network-based cortical volumetric measures. After performing this lesion correction procedure, we measured the surface area of lesion overlap with each network and the percent volume of each network affected by lesions. We identified 120 lesions that caused inaccuracies in the cortical surface in 46 patients. In these 46 patients, the most commonly lesioned networks were the limbic and default mode networks (95.7% each), followed by the executive control (78.3%), and salience (71.7%) networks. The limbic network had the largest average surface area of lesion overlap (4.4+/-3.7%) and the largest percent volume affected by lesions (12.7+/-9.7%). The lesion correction method has the potential to improve the accuracy of cortical volumetric measurements and permit inclusion of patients with lesioned brains in quantitative analyses, providing new opportunities to elucidate network-based mechanisms of neurological deficits in patients with TBI.

neuroscience↗